Specific Aim 3

Specific Aim 3

Examine interactions between T1D and T2D in Asian populations to uncover shared or distinct disease mechanisms.

Specific Aim 3 – Year 2 Highlights

  • Advanced genetic predicted ancestry, and polygenic risk studies across Stanford and external cohorts.
  • Expanded CGM, nutrition, meal-response, and precision metabolism collaborations.
  • Moved major collaborations, including KPRB, toward implementation and cross-cohort analysis.

Genetics of T1D, T2D, and Monogenic Diabetes among Asians in the Bay Area

Principal Investigators and Co-Principal Investigators: Anna L. Gloyn, DPhil; Everett Meyer, MD; David Maahs, MD, PhD, MA

Year 2 Highlights: This project continued advancing genetic analyses to support precision diagnostics for diabetes among Asian individuals in the Bay Area.

Making the correct diabetes diagnosis matters but can be difficult to get right as the clinical symptoms are very similar. Up to 5% of diabetes is due to a defect in a single gene, so called monogenic diabetes, and making a diagnosis of monogenic diabetes can change recommendations for how the patient should be treated, informs on prognosis and risk for family members. In European populations genetic risk scores for type 1 diabetes have been shown to be useful in identifying individuals at low risk for type 1 diabetes who may have monogenic diabetes. It is not clear how well these tests will work in more diverse patient populations.

The team has been recruiting newly diagnosed individuals with diabetes from the Stanford pediatric and adult clinics. At diagnosis all individuals are undergoing islet auto-antibody testing and having array genotyping performed. These analyses will help evaluate the performance of genetic risk scores across ancestry groups and inform future approaches to distinguishing Type 1, Type 2, and monogenic diabetes in both pediatric and adult populations. The latest genotyping data have been processed and are currently being analyzed bringing the dataset to ~500 individuals.

Looking Ahead: The team are now analyzing the entire data set and putting together their findings in a manuscript.

Genetic Ancestry, Clinical Heterogeneity, and Polygenic Risk in Diabetes in the Kaiser Permanente Research Bank (KPRB)

Principal Investigator and Collaborators: Anna L. Gloyn, DPhil; KPRB and ADVANCE collaborators

Year 2 Highlights: The KPRB project moved into implementation planning during Year 2, advancing a major collaboration focused on understanding diabetes heterogeneity in the KPRB and how this impacts response to treatment and diabetes complications.   This collaboration is expected to substantially expand ADVANCE’s ability to study diabetes heterogeneity in Asian American cohorts.

Looking Ahead: The team will finalize available data elements and genotyping data, complete code/QC handoff, run genetic ancestry and pPRS analyses, develop table shells and analytic protocols, and begin downstream analyses as data become available.

Evaluation of Care in Double Diabetes in Asian Americans

Co-Principal Investigators: Rayhan Lal, MD; Marina Basina, MD

Year 2 Highlights: This project continued evaluating care patterns and clinical complexity among Asian American patients with features of both Type 1 and Type 2 diabetes. During Year 2, Epic Cosmos antibody analysis moved forward with Seed Grant support and IRB approval was received. The project uses large-scale electronic health record data to better understand diabetes classification, care patterns, insulin resistance markers, and diagnostic overlap in Asian American patients.

Looking Ahead: Next steps include adapting Cosmos queries to identify Asian subgroups, insulin resistance markers, and clinically meaningful patterns that can support improved diagnosis and care for double diabetes.

Impact of NOURISH ADA/AHA Compliant Meals on Postprandial Glycemic Response Using Continuous Glucose Monitoring: A Crossover Quantitative and Qualitative Study

Principal Investigator: Minal Moharir, MD

Year 2 Highlights: The NOURISH study advanced its culturally modified nutrition and CGM-based research during Year 2. The IRB protocol was modified to expand recruitment channels, and seven participants were recruited. Chef recipe testing was completed with 29 South Asian and 15 Filipino recipes reviewed and tested, and NOURISH was integrated into the Tastermonial app. The PFEME seed grant was secured to support a continuing education course, and Stanford Continuing Studies invited NOURISH to be offered as a Winter course, with course details and description now in development alongside Chef Andrew Mayne and Dalia Perelman. The ADA Accelerator Award application was completed, and applications are in progress for PCORI, the Josiah Macy Jr. Foundation, and the Robert Wood Johnson Foundation. June 2026 updates introduced a proposed NOURISH x ADWC x Joslin collaboration to build a scalable, culturally grounded, AI-enabled diabetes nutrition ecosystem using validated education, recipes, behavioral care tools, and personalized nutrition approaches. This work connects clinical nutrition, CGM, digital health, and culturally responsive diabetes care.

Looking Ahead: The team will continue recruitment and study activities, hold follow-up collaboration meetings, share resource inventories, identify pilot opportunities, clarify IP/MOU frameworks, and develop a scalable roadmap or proposal.

PRECISE SG-100K/NUS CGM

Lead Postdoctoral Researcher and collaborators: Yue Wu, PhD; Michael Snyder, PhD; Krish Shah, MS; Lu Zhang, PhD; SG-100K/NUS collaborators

Year 2 Highlights: During Year 2, ADVANCE established and expanded collaboration with PRECISE-SG100K/NUS to leverage CGM, genomic, and clinical data for Asian-specific diabetes risk, metabolic traits, and meal-response research. The NUS study design includes clinical data, microbiome, lipidomics, metabolomics, genotyping, food logs, CGM, and wearable data. June updates reported three additional phenotyped Singapore datasets available for PRS analysis, with ADVANCE supporting local teams to run analyses.

Looking Ahead: Next steps include completing integrating PRS/pPRS with meal-response phenotypes, omics, and subgroup analyses, and identifying publication and cross-cohort replication opportunities.

Multiple cohorts related to NOURISH

Lead Postdoctoral Researcher and collaborators: Yue Wu, PhD and NOURISH-related collaborators

Year 2 Highlights: This Year 2 effort expanded the NOURISH-related research portfolio across multiple cohorts focused on meal-response patterns, nutrition, cardiometabolic health, and personalized diabetes prevention. The work aligns with broader ADVANCE efforts to use CGM and culturally tailored interventions to better understand postprandial glycemic response and metabolic health in Asian populations.

Looking Ahead: The team will define priority analyses, integrate cohort data, align NOURISH-related cohorts with AI-enabled nutrition tools and validated recipe resources, and identify pilot studies, publications, and grant opportunities.

Collaboration with Dr. Anna Gloyn

Lead Postdoctoral Researcher: Yue Wu, PhD

Year 2 Highlights: This collaboration continued integrating genetics, ancestry, and deep metabolic phenotype data to better understand diabetes heterogeneity in Asian populations. During Year 2, sub-Asian group information and ancestral estimation were completed, ratios of metabolic subtypes were generated, and analyses comparing polygenic risk scores with clinical measurements continued.

Looking Ahead: Next steps include refining PRS and clinical phenotype profiles and evaluating opportunities for cross-cohort replication.

Mitigator Cohort

Lead Postdoctoral Researcher: Yue Wu, PhD

Year 2 Highlights: The Mitigator Cohort was integrated into the broader Asian-specific meal-response, metabolic traits, and personalized mitigation of glucose excursion research portfolio during Year 2. This cohort creates opportunities to study factors associated with favorable metabolic health outcomes and metabolic resilience. By linking nutrition, glycemic response, and diabetes risk, this work contributes to ADVANCE’s broader goal of identifying protective and risk-related metabolic patterns in Asian populations.

Looking Ahead: Next steps include continuation of cohort collection.

Asian-Specific Meal Response & Metabolic Traits Analysis

Lead Postdoctoral Researcher and collaborators: Yue Wu, PhD, Anna L. Gloyn, DPhil, Lu Zhang, Phd, Han Sun, PhD, SG-100K collaborators

Year 2 Highlights: Asian-specific meal-response and metabolic trait analyses advanced as a distinct Year 2 project area supporting CGM, nutrition, and precision metabolism studies. June updates outlined a long-term Aim 3 vision for large-scale CGM with food-log and food-image data, model-assisted food logging, and personalized prediction of glycemic response. This work builds on ADVANCE’s focus on understanding how diabetes risk and metabolic response may differ across Asian subgroups and dietary patterns.

Looking Ahead: The team will advance integrated meal-response analyses, develop food-image and CGM forecasting models, refine large-scale study design, and identify publication and funding opportunities across meal-response and metabolic traits work.